We propose to continue our studies of the past eight years on the mechanisms by which large molecules get across capillary walls and are returned to the bloodstream by the lymphatics. We shall study the characteristics of the capillary wall as a molecular sieve using as test molecules the plasma proteins which are already present, and various exogenous test molecules of comparable molecular size (mostly things like Dextran and gelatin, which have been used clinically as plasma protein substitutes). Chemical and physiochemical procedures adapted over the past eight years will be used to measure and sort out these different molecules in samples of blood plasma and lymph obtained from anesthetized dogs. We shall test experimentally the effects of increasing capillary pressure and of increasing and decreasing plasma volume on blood-lymph transport in peripheral and visceral organs. We shall use animals prepared surgically for chronic collection of lymph in long-term studies of the effects of plasma volume changes on capillary permeability and of lymph removal from the interstitial space. The results of our experiments will add to our knowledge of plasma volume control in health and disease, and contribute to our ability to treat disturbances in fluid balance between the blood and extravascular fluids.